RT Journal Article
SR Electronic
T1 Autism-linked gene FoxP1 selectively regulates the cultural transmission of learned vocalizations
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.03.14.992016
DO 10.1101/2020.03.14.992016
A1 Francisco Garcia-Oscos
A1 Therese Koch
A1 Harshida Pancholi
A1 Massimo Trusel
A1 Vamsi Daliparthi
A1 Fatma Ayhan
A1 Marissa Co
A1 Danyal H. Alam
A1 Jennifer E. Holdway
A1 Genevieve Konopka
A1 Todd F. Roberts
YR 2020
UL http://biorxiv.org/content/early/2020/03/19/2020.03.14.992016.abstract
AB Autism spectrum disorders (ASD) are characterized by impaired learning of culturally transmitted behaviors like social skills, speech, and language1–3. These behaviors are learned by copying parents and other social models during development, a two-stage process that involves forming memories of appropriate behaviors during social experiences and then using those memories to guide imitation. How ASD-linked genes impair these often-intertwined aspects of learning is not known, thereby limiting our understanding of the developmental progression of ASD and the targeting of therapeutic interventions. Here we show that these aspects of learning are dissociable and that the ASD-linked gene FoxP1 selectively impairs learning from social experience, but not behavioral imitation. Haploinsufficiency of FOXP1 in humans causes FOXP1 syndrome, a neurodevelopmental disorder typified by severe disruptions in speech and language development, and other ASD-associated symptoms4,5. We tested how knockdown of FoxP1 (FP1-KD) affects the cultural transmission of vocal behaviors in zebra finches, a songbird that learns by memorizing and vocally copying the song of an adult ‘song-tutor’. We find that FP1-KD blocks song learning in juvenile birds by selectively impairing their ability to encode a memory during social experiences with a songtutor. These learning deficits are linked to disruptions in experience-driven structural and functional plasticity. However, if birds are exposed to tutor-song prior to FP1-KD, their ability to imitate that song during development is unaffected. Thus, FP1-KD impairs cultural transmission of vocalizations by disrupting the ability to form appropriate vocal memories, yet spares the ability to use previously acquired memories to guide vocal learning. This indicates that learning from social experience may be particularly vulnerable in FOXP1 syndrome.